Composite Biomaterials for Neurite Outgrowth Project Summary: Our long-term objective is twofold: to elucidate the cellular and molecular mechanisms that underlie axon guidance during development and after injury, and to develop biomaterial platforms to support and enhance axon growth. Our working hypothesis is that the combination of multiple growth- promoting cues will enable axon growth to overcome the local inhibitory environment (i.e., glial scar) that develops post-injury. To test this hypothesis will require new platforms to (1) deliver a combination of growth-promoting cues in a controllable and quantifiable manner; and (2) provide a means by which to test a stimulatory environment against an inhibitory environment. These platforms will make possible innovative experiments that will test for the first time how combinations of guidance cues promote axon growth in an inhibitory environment. Relevant to NIBIB's mission to improve health by promoting fundamental discoveries, design, and development in bioengineering, our objective is to correlate axon growth and direction to specific quantities and ratios of stimulatory and inhibitory cues, thus establishing the basis for new strategies for nerve regeneration. This innovative multidisciplinary proposal combines the complimentary expertise of the Principal Investigator in neuronal development, regeneration, and biomaterials and the Co-Investigator in electrochemistry, microfabrication, and surface characterization, to fabricate a platform capable of delivering precise quantities of both biological guidance cues and electrical stimulation (Aim 1). Aim 2 focuses on determining if specific stimulatory guidance cues (i.e., electrical stimulation, and laminin-1) are synergistic at enhancing neurite growth. Aim 3 focuses on determining how much stimulation is required for neurites to overcome an inhibitory environment (i.e., chondroitin sulfate proteoglycans). Relevance: Nerves fail to regenerate after injury and current medical practice is unable to manipulate effectively the process of nerve regeneration. The proposed research seeks to solve this problem by quantifying how multiple beneficial cues can help nerves to grow in an inhibitory environment such as a nerve injury site. [unreadable] [unreadable] [unreadable]